Human urinary composition controls antibacterial activity of siderocalin

Robin R. Shields-Cutler, Jan R. Crowley, Chia S. Hung, Ann E. Stapleton, Courtney C. Aldrich, Jonas Marschall, Jeffrey P. Henderson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here, we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine.

Original languageEnglish
Pages (from-to)15949-15960
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number26
DOIs
StatePublished - Jun 26 2015

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    Shields-Cutler, R. R., Crowley, J. R., Hung, C. S., Stapleton, A. E., Aldrich, C. C., Marschall, J., & Henderson, J. P. (2015). Human urinary composition controls antibacterial activity of siderocalin. Journal of Biological Chemistry, 290(26), 15949-15960. https://doi.org/10.1074/jbc.M115.645812